Hydroxyethylrutosides are semi-synthetic molecules that are made by reacting the phytochemical flavonoid rutin with ethylene oxide. See U.S. Pat. No. 3,420,815. Hydroxyethylrutosides have been used in Europe for the past forty years for chronic venous insufficiency and hemorrhoids under the tradenames VENORUTON® and PARAVEN™. The main components of VENORUTON® are 7-mono-hydroxyethylrutoside (also called MonoHER); 7,4′ dihydroxyethylrutoside; 7,3′,4′ trihydroxyethylrutoside (also called troxerutin); 5,7,3′,4′-tetrahydroxyethylrutoside; and 7,3′,4′-trihydroxyethylquercetin. See Kendall, Br. J. Pharmacol., 1993, 110, 199-206 and van Acker, Br. J. Pharmacol., 1995, 115, 1260-64.
VENORUTON® is often administered several times a day in pregnant women. Titapant, J. Med. Assoc. Thai, 2001, October 84 (10) 1395-400 (twice daily to pregnant women for hemorrhoids); Wijayanegara, J. Int. Med. Res., 1992 Feb., 20, 1, 54-60 (97 pregnant women; twice daily); Bergstein, J. Intl. Med. Res., 1975, 3, 189-93 (69 total double blind with pregnant women; 28+ weeks, 3 times daily).